期刊文献+

非小细胞肺癌组织中Skp2的表达及其与p27^(kip1)和Ki-67蛋白表达的关系 被引量:7

Expression of Skp2 in non-small cell lung cancer and its relationship with p27^(kip1) and Ki-67 protein expressions
下载PDF
导出
摘要 目的:探讨Skp2的表达在非小细胞肺癌(nonsmallcelllungcancer,NSCLC)发生发展中的作用,及其与p27kip1和Ki67蛋白表达的关系。方法:应用免疫组化SP法检测Skp2、p27kip1和Ki67三种蛋白在60例NSCLC和20例正常支气管黏膜上皮组织中的表达。结果:NSCLC组织中Skp2蛋白表达的阳性率为48.33%(29/60),显著高于正常支气管黏膜上皮组织中的表达,P=0.000。Skp2的表达与肿瘤的组织学类型、肿瘤细胞的分化程度、TNM分期、淋巴结转移和患者吸烟与否显著相关,P值分别为0.038、0.005、0.019、0.010和0.002,但与患者的年龄及性别无关,P值分别为0.833和0.281。NSCLC组织中Skp2表达与p27kip1表达呈显著负相关,P=0.001;而与Ki67表达呈显著正相关,P=0.027。结论:Skp2在NSCLC组织中表达是上调的,可能是通过作用于细胞周期调控蛋白p27kip1,加速了对p27kip1泛素化依赖的蛋白降解,使其表达及代谢发生异常,导致细胞周期失控并促进细胞异常增殖,从而参与了NSCLC的发生和发展。 OBJECTIVE:To investigate the expression of Skp2 and its relationship with expressions of p27^kip1 and Ki-67 proteins in human non-small cell lung cancer(NSCLC). METHODS: Immunohistochemical methods were applied to detect the expressions of Skp2, p27^kip1 and Ki-67 proteins in 60 surgical specimens from NSCLC patients and 20 normal bronchial epithelium. RESULTS: In NSCLC, the positive rate of Skp2 protein was 48. 33% (29/60). Which was obviously higher than that in normal bronchial epithelium, P = 0. 000. There was no relationship between Skp2 expression and age (P = 0. 833) or sex (P=0.281),respectively;otherwise, there was closely rdationship between Skp2 expression and histological subtype, cellular differentiation, TNM stage, lymph node metastasis, smoking, P= 0. 038, 0. 005, 0. 019, 0. 010 and 0. 002, respectively. Expression of Skp2 was negatively correlated with expression of p27^kip1 , P = 0. 001 ; but was positively correlated with expression of Ki-67, P = 0. 027. CONCLUSlONS: Expression of Skp2 is up-regulated significantly in NSCLC compared with normal bronchial epithelium, and overexpression of Skp2 reduces the protein level of p27^kip1 through ubiquitin-dependent degradation and causes disruption of cell cycle control and enhancement of the proliferative activity, indicating Skp2 playes an important role in oncogenesis and development of NSCLC.
出处 《中华肿瘤防治杂志》 CAS 2006年第2期93-96,共4页 Chinese Journal of Cancer Prevention and Treatment
基金 国家自然科学基金资助项目(39870305)
关键词 非小细胞肺/病理学 S期激酶相关蛋白类/遗传学 Ki-67抗原/生物合成 细胞周期蛋白质依赖激酶类/代谢 免疫组织化学 carcinoma, non-small cell lung/pathology S-phase kinase-associated proteins/genetics Ki-67 antigen/biosynthesis cyclin-dependent kinases/metabolism immunohistochemistry
  • 相关文献

参考文献13

  • 1Masuda T A, Inoue H, Sonoda H, et al. Clinical and biological significance of s-phase kinase-associated protein 2(skp2)gene expression in gastric carcinoma: modulation of malignant phenotype by skp2 overexpression possible via p27 proteolysis[J].Cancer Res, 2002,62(13):3819-3825.
  • 2Signoretti S, Di Marcotullio L, Riehardson A, et al. Oncogenic role of the ubiquitin ligase subunit skp2 in human breast cancer [J]. J Clin Invest,2002,110(5):633-641.
  • 3Yang G, Ayala G, Marzo A D, et al. Elevated skp2 protein expression in human prostate cancer: associated with loss of the cyclin-dependent kinase inhibitor p27 and PTEN and with reduced recurrence-free survival[J]. Clin Cancer Res,2002,8(11) :3419-3426.
  • 4Travis W D, Colby T V, Corrin B, et al. Histological typing of lung and pleural turnouts, International histological classification of tumours[M]. 3rd ed. Berlin: Springer, 1999.
  • 5Sobin L H, Wittekind C. UICC T N M classification of malignant tumous[M]. 5th ed. New York: Wiley-Liss, 1997 : 93-97.
  • 6陈洪雷,刁路明,陈德基,李红钢,陈福春,刘铭球.大鼠肺癌癌变过程中G_1/S期调节基因的动态表达[J].中华结核和呼吸杂志,2002,25(6):376-377. 被引量:5
  • 7Demetrick D J, Zhang H, Beach D H. Chromosomal mapping of the genes for the human CDK2/cyclinA-associated proteins p19(SKP1A and SKP1B) and p45(SKP2)[J]. Cytogenet Cell Genet, 1996, 73(1-2):104-107.
  • 8Zhu C Q, Blackhall F H, Pintilie M, et al. Skp2 gene copy number aberrations are common in non-small-cell lung carcinoma, and its overexpression in tumors with ras mutation is a poor prognostic marker[J]. Clin Cancer Res, 2004, 10(6) : 1984-1991.
  • 9Yokoi S, Yasui K, Saito-Ohara F, et al. A novel target gene skp2 with the 5p13 amplicon that is frequently detected in small cell lung cancer[J]. Am J Pathol,2002,161(1):207-216.
  • 10Imaki H, Nakayama K, Delehouzee S, et al. Cell cycle-dependent regulation of the Skp2 promoter by GA-binding protein[J].Cancer Res,2003, 63(15) :4607-4613.

二级参考文献1

  • 1季代金 朱立平 等.原位杂交免疫细胞组织化学和免疫PCR技术.免疫学常用实验方法[M].北京:人民军医出版社,2000.438-441.

共引文献4

同被引文献70

引证文献7

二级引证文献16

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部